Skip to main content
Journal cover image

An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug.

Publication ,  Journal Article
Ozer, I; Slezak, A; Sirohi, P; Li, X; Zakharov, N; Yao, Y; Everitt, JI; Spasojevic, I; Craig, SL; Collier, JH; Campbell, JE; D'Alessio, DA ...
Published in: Biomaterials
March 2023

Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. However, the improvement in the plasma half-life of PEGylated drugs' is at an asymptote because the development of branched PEG has only had a modest impact on pharmacokinetics and pharmacodynamics. Here, we developed an injectable PEG-like conjugate that forms a subcutaneous depot for the sustained delivery of biologics. The PEG-like conjugate consists of poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) conjugated to exendin, a peptide drug used in the clinic to treat type 2 diabetes. The depot-forming exendin-POEGMA conjugate showed greater efficacy than a PEG conjugate of exendin as well as Bydureon, a clinically approved sustained-release formulation of exendin. The injectable depot-forming exendin-POEGMA conjugate did not elicit an immune response against the polymer, so that it remained effective and safe for long-term management of type 2 diabetes upon chronic administration. In contrast, the PEG conjugate induced an anti-PEG immune response, leading to early clearance and loss of efficacy upon repeat dosing. The exendin-POEGMA depot also showed superior long-term efficacy compared to Bydureon. Collectively, these results suggest that an injectable POEGMA conjugate of biologic drugs that forms a drug depot under the skin, providing favorable pharmacokinetic properties and sustained efficacy while remaining non-immunogenic, offers significant advantages over other commonly used drug delivery technologies.

Duke Scholars

Published In

Biomaterials

DOI

EISSN

1878-5905

Publication Date

March 2023

Volume

294

Start / End Page

121985

Location

Netherlands

Related Subject Headings

  • Polyethylene Glycols
  • Peptides
  • Humans
  • Exenatide
  • Diabetes Mellitus, Type 2
  • Delayed-Action Preparations
  • Biomedical Engineering
  • Antigens
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ozer, I., Slezak, A., Sirohi, P., Li, X., Zakharov, N., Yao, Y., … Chilkoti, A. (2023). An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug. Biomaterials, 294, 121985. https://doi.org/10.1016/j.biomaterials.2022.121985
Ozer, Imran, Anna Slezak, Parul Sirohi, Xinghai Li, Nikita Zakharov, Yunxin Yao, Jeffrey I. Everitt, et al. “An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug.Biomaterials 294 (March 2023): 121985. https://doi.org/10.1016/j.biomaterials.2022.121985.
Ozer I, Slezak A, Sirohi P, Li X, Zakharov N, Yao Y, et al. An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug. Biomaterials. 2023 Mar;294:121985.
Ozer, Imran, et al. “An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug.Biomaterials, vol. 294, Mar. 2023, p. 121985. Pubmed, doi:10.1016/j.biomaterials.2022.121985.
Ozer I, Slezak A, Sirohi P, Li X, Zakharov N, Yao Y, Everitt JI, Spasojevic I, Craig SL, Collier JH, Campbell JE, D’Alessio DA, Chilkoti A. An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug. Biomaterials. 2023 Mar;294:121985.
Journal cover image

Published In

Biomaterials

DOI

EISSN

1878-5905

Publication Date

March 2023

Volume

294

Start / End Page

121985

Location

Netherlands

Related Subject Headings

  • Polyethylene Glycols
  • Peptides
  • Humans
  • Exenatide
  • Diabetes Mellitus, Type 2
  • Delayed-Action Preparations
  • Biomedical Engineering
  • Antigens